Autologous Cord Blood Cell Therapy for Neonatal Encephalopathy

A Pilot Feasibility and Safety Study of Autologous Umbilical Cord Blood Cell Therapy in Infants With Neonatal Encephalopathy

This is a pilot study to test feasibility and safety of intravenous infusion of autologous umbilical cord blood cells in the first 72 hours after birth if a neonate is born with signs of encephalopathy.

Study Overview

• Status: Completed
• Conditions: Neonatal Encephalopathy; Hypoxic-ischemic Encephalopathy
• Intervention / Treatment: Other: Autologous umbilical cord blood cells

Detailed Description

This is a multicenter pilot study to evaluate the feasibility and safety of intravenous infusions of autologous (the patient's own) umbilical cord blood cells in term gestation newborns with neonatal encephalopathy (hypoxic-ischemic encephalopathy). If a neonate is born with signs of moderate to severe encephalopathy and cooled for the encephalopathy, the neonate can receive their own non-cryopreserved volume- and red blood cell-reduced cord blood cells. The cord blood cells are divided into 3 doses and infused at 12-24, 36-48, and 60-72 hours after the birth. Infants will be followed for safety and neurodevelopmental outcome up to 18 months.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan, 534-0021
    • Osaka City General Hospital
  • Osaka, Japan, 545-8585
    • Osaka City University
  • Osaka, Japan, 533-0032
    • Yodogawa Christian Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
      • Nagoya University Hospital
  • Okayama
    • Kurashiki, Okayama, Japan, 710-8602
      • Kurashiki Central Hospital
  • Saitama
    • Kawagoe, Saitama, Japan, 350-0495
      • Saitama Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 day (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Infants are eligible if they meet all the following inclusion criteria except 4.

1. ≥36 weeks gestation
2. Either a 10-minute Apgar score ≤5, continued need for resuscitation for at least 10 minutes, or severe acidosis, defined as pH <7.0 or base deficit ≥16 mmol/L in a sample of umbilical cord blood or any blood during the first hour after birth
3. Moderate to severe encephalopathy (Sarnat II to III)
4. A moderately or severely abnormal background amplitude-integrated EEG (aEEG) voltage, or seizures identified by aEEG, if monitored
5. Up to 24 hours of age
6. Autologous umbilical cord blood available to infuse within 3 days after birth
7. A person with parental authority must have consented for the study.

Exclusion Criteria:

1. Known major congenital anomalies, such as chromosomal anomalies, heart diseases
2. Major intracranial hemorrhage identified by brain ultrasonography or computed tomography
3. Severe growth restriction, with birth-weight less than 1800 g
4. Severe infectious disease, such as sepsis
5. Hyperkalemia
6. Outborn infants (Infants born at hospitals other than the study sites)
7. Volume of collected cord blood <40 ml
8. Infants judged critically ill and unlikely to benefit from neonatal intensive care by the attending neonatologist

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cell therapy; Infants who are born at the study sites, have moderate to severe encephalopathy, and have cord blood available for infusion	Other: Autologous umbilical cord blood cells; Autologous non-cryopreserved volume- and red blood cell-reduced cord blood cells will be intravenously infused

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse event rates	Adverse event rates (combined rate of death, continuous respiratory support, and continuous use of vasopressor) will be compared between the cell recipients and historical controls at 30 days of age.	first 30 postnatal days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy	Neuroimaging at 12 months of age and neurodevelopmental function at 18 months of age will be compared between the cell recipients and historical controls.	18 months

Collaborators and Investigators

• Sponsor: Neonatal Encephalopathy Consortium, Japan
• Collaborators: National Cerebral and Cardiovascular Center; Nagoya University; Tokyo Women's Medical University; Tokyo University; Osaka City University; Saitama Medical University; Kurashiki Central Hospital; Osaka City General Hospital; Yodogawa Christian Hospital; National Center for Child Health and Development, Japan
• Investigators: Study Director: Haruo Shintaku, MD, PhD, Osaka City University

Publications and helpful links

General Publications

• Tsuji M, Taguchi A, Ohshima M, Kasahara Y, Sato Y, Tsuda H, Otani K, Yamahara K, Ihara M, Harada-Shiba M, Ikeda T, Matsuyama T. Effects of intravenous administration of umbilical cord blood CD34(+) cells in a mouse model of neonatal stroke. Neuroscience. 2014 Mar 28;263:148-58. doi: 10.1016/j.neuroscience.2014.01.018. Epub 2014 Jan 18.
• Ohshima M, Taguchi A, Tsuda H, Sato Y, Yamahara K, Harada-Shiba M, Miyazato M, Ikeda T, Iida H, Tsuji M. Intraperitoneal and intravenous deliveries are not comparable in terms of drug efficacy and cell distribution in neonatal mice with hypoxia-ischemia. Brain Dev. 2015 Apr;37(4):376-86. doi: 10.1016/j.braindev.2014.06.010. Epub 2014 Jul 14.
• Taguchi A, Soma T, Tanaka H, Kanda T, Nishimura H, Yoshikawa H, Tsukamoto Y, Iso H, Fujimori Y, Stern DM, Naritomi H, Matsuyama T. Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest. 2004 Aug;114(3):330-8. doi: 10.1172/JCI20622.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (ACTUAL): October 1, 2017
• Study Completion (ACTUAL): July 1, 2019

Study Registration Dates

• First Submitted: October 1, 2014
• First Submitted That Met QC Criteria: October 1, 2014
• First Posted (ESTIMATE): October 3, 2014

Study Record Updates

• Last Update Posted (ACTUAL): October 29, 2019
• Last Update Submitted That Met QC Criteria: October 28, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: neonates; neonatal encephalopathy; hypoxic-ischemic encephalopathy; newborn infants; umbilical cord blood cells
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Hypoxia; Hypoxia, Brain; Brain Ischemia; Brain Diseases; Hypoxia-Ischemia, Brain
• Other Study ID Numbers: UMIN000014903